Calmodulin (CaM) has been isolated from axenized trophozoites of G. lamblia and purified by gel electrophoresis, gel permeation, and ion exchange chromatography. The parasite CaM has properties characteristic of Cam isolated from other eukaryotes: (a) an apparent molecular weight of 16.7 kd, (b) activation of bovine cyclic AMP phosphodiesterase in a calcium-dependent manner, and (c) sensitivity to known CaM antagonists. Its amino acid composition is similar to mammalian CaM; yet some distinct differences in amino acid content are evident. The membranebound Ca2+-dependent ATPase of G. lamblia has been characterized, and found to be sensitive to inhibitors of CaM. Two novel enzymes of aerobic metabolism of Entamoeba histolytica were found in studies initiated this year: (1) a Ca2+-activated NADPH dehydrogenase (previously reported only in plants), and (2) a highly active Mn2+-dependent (Km = 5 MuM) pyridine nucleotide dehydrogenase specific for NADPH, Mn2+ and quinone electron acceptors. Biochemical and pharmacological studies were initiated on Trypanosoma cruzi with an examination of the effects of tricyclic antidepressant drugs on the in vitro growth of the parasite. Similar to our previous findings with the enteric protozoa, chlorimipramine was more toxic to the trypanosomes than was the parent compound imipramine (10 vs. 50 MuM). Morphological changes were clearly evident in the drug-treaded parasites. Studies of mammalian bioenergetics centered on the effects of diflusinal, a difluorophenyl derivative of salicylic acid, on oxidative phosphorylation. The drug has powerful uncoupling capacity, releasing respiratory control and impeding synthesis of ATP in rat liver mitochondria at low concentrations (IC50 = 20 MuM). This is another example where substitution by a halogen atom (flourine) increases the pharmacological potency of the parent compound (salicylic acid itself is virtually devoid of uncoupling properties).